Claims
- 1. A synthetic unimolecular. double-stranded oligonucleotide library comprising a plurality of different members. each member having the formula:
- 2. A library in accordance with claim 1, wherein L2 is a member selected from the group consisting of an alkylene group, a polyethyleneglycol group, a polyalcohol group, a polyamine group and a polyester group.
- 3. A library in accordance with claim 1, wherein L2 is a polyethylene glycol group.
- 4. A library in accordance with claim 1, wherein X1 and X2 are complementary oligonucleotides each comprising of from 6 to 30 nucleic acid monomers.
- 5. A library in accordance with claim 1, wherein said solid support is a silica support and L1 comprises an aminoalkylsilane and from 1 to 4 hexaethyleneglycols.
- 6. A library in accordance with claim 1, wherein said solid support is a silica support, L1 comprises an aminoalkylsilane and from 1 to 4 hexaethyleneglycols, L2 is a polyethyleneglycol group and X1 and X2 are complementary oligonucleotides each comprising of from 6 to 30 nucleic acid monomers.
- 7. A synthetic unimolecular, double-stranded oligonucleotide library of claim 1, wherein a portion of said double-stranded oligonucleotides formed by X1 and X2 further comprise a bulge.
- 8. A synthetic unimolecular, double-stranded oligonucleotide library of claim 1, wherein a portion of said double-stranded oligonucleotides formed by X1 and X2 further comprise a loop.
- 9. A synthetic unimolecular, double-stranded nucleic acid library of claim 1, wherein each member further comprises an identifier tag, said identifier tag identifying the sequence of said unimolecular, double-stranded nucleic acid.
- 10. A synthetic unimolecular, double-stranded nucleic acid library of claim 1, wherein said solid support comprises a first bead linked to a second bead, wherein the double-stranded nucleic acid is attached to the first bead and an identifier tag is attached to the second bead.
- 11. A method of forming a plurality of diverse unimolecular, double-stranded oligonucleotides on a solid support having optional spacers, said support comprising a surface with a plurality of preselected regions, said method comprising:
(a) forming on each of said preselected regions a different first oligonucleotide, each of said first oligonucleotides comprising of from 6 to 30 monomers; (b) attaching to the distal end of each of said first oligonucleotides of step (a) a linking group; and (c) forming on the distal end of each of said linking groups a second oligonucleotide, wherein each of said second oligonucleotides is complementary to said first oligonucleotide which is attached within the same preselected region, and wherein said linking groups have sufficient length such that said first and second oligonucleotides form a unimolecular, double-stranded oligonucleotide.
- 12. A method in accordance with claim 11, wherein said method of construction of step (a) and step (b) is by light-directed synthesis.
- 13. A method of screening a sample for a species capable of binding to double-stranded DNA comprising:
contacting said sample with a solid support comprising unimolecular, double-stranded DNA attached thereon, each of said attached DNA independently having the formula;—X11—L—X12 wherein,
X11 and X12 are complementary oligonucleotides; and L is a linking group having sufficient length such that X11 and X12 form said attached unimolecular, double-stranded DNA, to produce at least one bound pair comprising said species and one of said attached unimolecular, double-stranded DNA; and identifying said bound pair.
- 14. A method in accordance with claim 11, wherein said species is a member selected from the group consisting of a drug, a protein and an RNA molecule.
- 15. A method of screening a sample for a species capable of binding to double-stranded DNA comprising:
contacting said sample with a solid support comprising a unimolecular, double-stranded DNA attached thereon, said attached DNA having the formula;—X11—L—X12 wherein,
X11 and X12 are complementary oligonucleotides; and L is a linking group having sufficient length such that X11 and X12 form said attached unimolecular, double-stranded DNA, to produce a bound pair comprising said species and said attached unimolecular, double-stranded DNA; and identifying said bound pair.
- 16. A synthetic conformationally-restricted probe library comprising a plurality of members, each of said members comprising a solid support attached to an oligomer having the formula:
- 17. A synthetic library in accordance with claim 16, wherein each of said probes is a peptide having of from about 4 to about 12 amino acids.
- 18. A synthetic library in accordance with claim 16, wherein each member further comprises an intercalating dye.
- 19. A method of synthesizing a library of conformationally-restricted probes on a solid support having optional spacers, said support comprising a surface with a plurality of preselected regions, said method comprising:
(a) forming on each of said preselected regions a first oligonucleotide, each of said first oligonucleotides comprising of from 6 to 30 monomers; (b) attaching to the distal end of each of said first oligonucleotides of step (a) a probe; and (c) forming on the distal end of each of said probes a second oligonucleotide, wherein each of said second oligonucleotides is complementary to said first oligonucleotide which is attached within the same preselected region, and wherein said probes have sufficient length such that said first and second oligonucleotides form a unimolecular, double-stranded oligonucleotide thereby conformationally-restricting said probes.
- 20. A method in accordance with claim 19, wherein said method of construction of step (a) and step (b) is by light-directed synthesis.
- 21. A method of screening a sample for a species capable of binding to a conformationally-restricted probe comprising:
contacting said sample with a solid support comprising conformationally-restricted probes attached thereon, each of said attached probes independently having the formula;—X11—Z—X12 wherein,
X11 and X12 are complementary oligonucleotides; and Z is a probe having sufficient length such that X11 and X12 form a double-stranded oligonucleotide portion of said conformationally-restricted probe, to produce at least one bound pair comprising said species and one of said attached conformationally-restricted probes; and identifying said bound pair.
- 22. An adhesive for use in biological applications comprising a first surface having a plurality of attached oligonucleotides and a second surface having a plurality of attached oligonucleotides, wherein the oligonucleotides of said first surface are substantially complementary to the oligonucleotides of said second surface.
GOVERNMENT RIGHTS
[0001] Research leading to the invention was funded in part by NIH Grant No. ______, and the government may have certain rights to the invention.
Divisions (1)
|
Number |
Date |
Country |
Parent |
08644093 |
May 1996 |
US |
Child |
09054969 |
Apr 1998 |
US |